Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by chronic anovulation, hyperandrogenism, and insulin resistance with an estimated prevalence of 5-10% among all women. Family studies have indicated a genetic predisposition to the development of PCOS and several candidate PCOS susceptibility genes have been explored. Thus far, pedigree studies have mainly focused on steroidogenic pathway dysfunction in women with little success in determining a genetic basis for PCOS. It has more recently been postulated that insulin resistance, rather than hyperandrogenism, is the central defect in PCOS. Peroxisome proliferator-activated receptor gamma (PPAR [gamma]) has been indicated as a potential candidate gene for insulin resistance in Type 2 diabetes. No studies to date have focused on the PPAR. pathway and insulin resistance in PCOS probands and their family members. Given the high prevalence of PCOS and its association with coronary heart disease, PCOS may represent the largest, unique group of women at high-risk for the development of coronary heart disease (CHD). Thus understanding the etiology of PCOS may have a large public health impact for women. This pilot study will examine extended pedigrees by analyzing linkage using both parametric and non-parametric methods in five multigeneration, multiplex families (N= 125). We will explore genetic mechanisms through the following specific aims by: (1) demonstrating our ability to enroll both PCOS probands and their multi generation, multiplex family members to study insulin resistance markers in families with PCOS and (2) genotyping five probands and their multigeneration, multiplex family members for single nucteotide polymorphisms (SNPs) at or near candidate genes P12A and IRS-1 and microsatellite markers near candidate genes lipoprotein lipase and acetyI-CoA carboxylase, to test for linkage of PCOS with these candidate genes.